Circulatory disease mortality and diabetes incidence in 27 families with Friedreich ataxia

Friedreich ataxia (FRA) is an autosomal recessive neuromuscular disorder in which nearly all affected homozygotes eventually develop significant cardiomy-opathy and a substantial proportion also develop diabetes mellitus. Diabetes and early heart disease have been observed previously in close blood relatives of FRA patients. To test the hypothesis that FRA heterozygotes may have elevated rates of heart disease mortality and diabetes incidence, we compared the rates of these conditions in 1,191 adult blood relatives to those in 745 nonblood relative spouse controls in 27 families of FRA patients.

We found no evidence for an excess of diabetes in the blood relatives. For three broad categories of circulatory disease mortality, the FRA blood relatives had significantly higher rates than the spouse controls. However, when each relative's prior probability of heterozygosity for the FRA gene was taken into account, the resulting estimates of relative risk of dying from circulatory disease for FRA heterozygotes compared to nonheterozygotes were not significantly elevated. Since the latter analysis provides the best test of the hypothesis, our data did not strongly support the hypothesis that FRA heterozygotes are at increased risk of cardiac death.